Frequent PLAG1 Gene Rearrangements in Skin and Soft Tissue Myoepithelioma (ME) with Ductal Differentiation
Cristina R Antonescu, Lei Zhang, Sung Yun Shao, Christopher D Fletcher. Memorial Sloan Kettering Cancer Center, New York, NY; Brigham & Women's Hospital, Boston, MA
Background: A subset of cutaneous and superficial ME tumors display a distinct ductal component and closely resemble mixed tumors/pleomorphic adenomas of salivary gland. As PLAG1 and HMGA2 gene rearrangements are the most common genetic events in pleomorphic adenomas, we sought to investigate if these abnormalities are also present in the skin/soft tissue ME lesions. In contrast, half of the deep-seated soft tissue ME tumors lacking ductal differentiation are known to be genetically unrelated, showing EWSR1 gene rearrangements.
Design: FISH analysis to detect PLAG1 and HMGA2 gene abnormalities was performed in 33 ME tumors, 8 from skin and 25 from soft tissue, lacking EWSR1 gene rearrangements. For the PLAG1 rearranged tumors, FISH and RACE was performed to identify potential fusion partners, including CTNNB1 (beta-catenin) on 3p21 and LIFR (leukemia inhibitory factor receptor) on 5p13.
Results: Recurrent PLAG1 gene rearrangement by FISH was detected in 11 (33%) lesions, including 2 (25%) in the skin and 9 (36%) in the soft tissue. All were classified as benign morphologically and all except one showed abundant tubulo-ductal differentiation (comprising 10/22 [45%] of all tumors with ductal structures). A PLAG1-LIFR fusion was detected by RACE and then confirmed by FISH in one soft tissue ME tumor with tubular formation. No CTNNB1 or LIFR abnormalities were detected in any of the remaining PLAG1-rearranged tumors. No HMGA2 gene abnormalities were detected in any of the 22 ME lesions tested.
Conclusions: A subset of cutaneous and soft tissue ME tumors appear genetically linked to their salivary gland counterparts, displaying frequent PLAG1 gene rearrangements and occasionally PLAG1-LIFR fusion.
Category: Bone & Soft Tissue
Tuesday, March 20, 2012 8:45 AM
Platform Session: Section G, Tuesday Morning